Lipids are central to the control of cellular function and disease. The scope of the actions of lipids has only recently become widely recognized, going beyond an appreciation for their well-established roles in energy metabolism and membrane structure. Changes in the levels of one lipid class not only affect the other members of that class, but can also strongly affect other classes as well. While investigators have been able to monitor concurrent changes in a few members of one lipid class, no comprehensive strategy has emerged for characterizing the global changes in lipid metabolites ("lipidomics"), in contrast to the global level analyses routinely carried out for nucleic acids (genomics) and proteins (proteomics). We outline a new strategy that would lead to the integration of lipids into the general focus of 21st Century biology; namely, into a fully quantitative systems-level biology. Our collaboratory, the National Alliance for the Comprehensive Characterization of Lipid Function, will develop an integrated Lipid Metabolomics and Proteomics System, termed LIPID MAPS. The specific aim of LIPID MAPS for this grant period is to develop the requisite technology and conduct an interconnected research program that will yield lipidomics as a fully established research strategy. Through using a common set of biological, biochemical and analytical technologies, and a rich information infrastructure, we will be able to connect and integrate the results from individual research units, and then share our findings with the entire research community to enable a much broader effort. Numerous physiological processes involve changes in tissue levels of lipids, which also relate to lipid involvement in disease. Thus, lipids play a central role in many diseases, from inflammatory processes to arteriosclerosis, Alzheimer's disease, cancer and stroke. Yes, in contrast to other macromolecules, lipids have remained such a challenge that no coordinated national program for their study exists. We believe that the experimental technologies are now in hand for a functional characterization of LIPID MAPS. This functional characterization, coupled with our knowledge of other macromolecules and cell processes, will enable the community as a whole to establish predictive models for homeostasis and drug responses in disease states.